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[Risk perception and strategies for mass communication on dengue in the Americas].

Dengue is clearly a very serious public health problem. In the Americas the number of dengue cases has been increasing since the 1960s, and outbreaks of the disease have been occurring more frequently. Furthermore, the density of infestation with the disease vector, the Aedes aegypti mosquito, is high in the Americas. The general strategy for preventing and controlling dengue and dengue hemorrhagic fever is based on promoting behavior changes that lead to incorporating the community in controlling the disease, particularly the vector. In order to achieve this, mass communication programs on dengue should have two primary aims: converting information into practice and encouraging the community to take over prevention and control measures. The new generation of programs should be designed based on the local sanitation structure (water distribution and waste disposal) as well as information on community organizations and the roles of different family members. Furthermore, the new programs should incorporate all the following ten components: epidemiological surveillance, intersectoral actions, community participation, managing the environment and basic services, patient care, case reporting, education, using insecticides and vector control, training, and preparing for emergencies. Communication should be aimed at modifying the behavior of individuals and the community by empowering them to carry out prevention and control measures.

Attitude to Health↗

Pathologic study of a fatal case of dengue-3 virus infection in Rio de Janeiro, Brazil.

Dengue hemorrhagic fever (DHF) is a severe febrile disease, characterized by abnormalities in hemostasis and increased vascular permeability, which in some cases results in hypovolemic shock syndrome and in dengue shock syndrome. The clinical features of DHF include plasma leakage, bleeding tendency and liver involvement. We studied the histopathological features of a fatal case of dengue-3 virus infection. The patient, a 63-year old male, presented with an acute onset of severe headache, myalgia and maculopapular rash. Tissue fragments (liver, spleen, lung, heart, kidney and lymph nodes) were collected for light microscopy studies and stained by standard methods. Histopathology revealed severe tissue damage, caused by intense hemorrhage, interstitial edema and inflammation. Some tissue sections were also processed with the immunoperoxidase reaction, which revealed the dengue viral antigen. Dengue-3 virus was isolated and identified with electron microscopy in a C6/36 cell culture inoculated with the patient's serum. Viral particles were detected in the infected cell culture.

Fatal Outcome↗

Dengue fever among Swedish tourists.

Serologically confirmed cases of dengue fever among Swedish tourists were studied retrospectively. Dengue fever was found to be the most commonly diagnosed imported arbovirus disease in Sweden during the period December 1989-November 1990. 24 cases were diagnosed. The geographical epidemiology showed that 17/23 who answered a questionnaire were infected in Thailand, most often during spring and early summer. 17 patients were admitted to hospital. All patients had high fever. Other common symptoms were myalgia, headache, fatigue/prostration and erythema. All patients but 1 with a long-standing ataxia recovered without sequelae. Low white blood cell and platelet counts were registered in all sampled patients. Depressed sodium levels and elevated liver enzymes were seen regularly. Dengue virus type 1 was isolated from 2 patients who suffered from dengue haemorrhagic fever grade II in the course of their primary dengue virus infection.

Adult↗

Ocular manifestations of dengue fever in an East Indian epidemic.

BACKGROUND: The incidence and geographic distribution of dengue has increased dramatically in recent years. Previously, ocular findings in dengue fever were considered rare. We report a spectrum of ocular manifestations of this potentially fatal disease and its association with laboratory parameters. METHODS: 134 patients hospitalized with a diagnosis of dengue fever during an epidemic were included. Systemic and ophthalmic examinations were completed on all patients. RESULTS: The mean age was 31.3 years and 63.4% were males. All patients presented with fever. Six (4.5%) patients had retrobulbar pain and none of the patients presented with any visual complaints. Ocular findings were present in 54 (40.3%) patients. Subconjunctival haemorrhage was the commonest eye finding seen in 50 patients, of whom 84% had characteristic petechial type of haemorrhages. Fundus findings present in 10 (7.5%) patients included dilatation and tortuosity of vessels, superficial retinal haemorrhages, cotton-wool spots, and hard exudates; the macula, however, was spared in all patients. Only 6 of the patients with posterior segment involvement returned for follow-up examination and it was found that retinal changes had resolved without any specific treatment within 2 to 8 weeks time. Of all laboratory parameters evaluated, marked thrombocytopenia (platelet count <50,000/microL) emerged to be significantly associated with ocular haemorrhage. INTERPRETATION: Multiple subconjunctival haemorrhages, especially petechial type, are a common manifestation of dengue infection. Dengue fever patients with marked thrombocytopenia are predisposed to spontaneous ocular haemorrhages.

Adolescent↗

Dengue risk among visitors to Hawaii during an outbreak.

Despite the high rates of dengue in many tropical destinations frequented by tourists, limited information is available on the risk for infection among short-term visitors. We retrospectively surveyed 4,000 persons who arrived in Hawaii during the peak of the 2001-2002 dengue outbreak and collected follow-up serologic test results for those reporting denguelike illness. Of 3,064 visitors who responded, 94 (3%) experienced a denguelike illness either during their trip or within 14 days of departure; 34 of these persons were seen by a physician, and 2 were hospitalized. Twenty-seven visitors with denguelike illness provided a serum specimen; all specimens were negative for anti-dengue immunoglobulin G antibodies. The point estimate of dengue incidence was zero infections per 358 person-days of exposure with an upper 95% confidence limit of 3.0 cases per person-year. Thus, the risk for dengue infection for visitors to Hawaii during the outbreak was low.

Dengue↗

Dengue virus-reactive CD8+ T cells display quantitative and qualitative differences in their response to variant epitopes of heterologous viral serotypes.

Reactivation of serotype cross-reactive CD8+ memory T lymphocytes is thought to contribute to the immunopathogenesis of dengue disease during secondary infection by a heterologous serotype. Using cytokine flow cytometry, we have defined four novel HLA-A*02-restricted dengue viral epitopes recognized by up to 1.5% of circulating CD8+ T cells in four donors after primary vaccination. All four donors had the highest cytokine response to the epitope NS4b 2353. We also studied the effect of sequence differences in heterologous dengue serotypes on dengue-reactive CD8+ memory T cell cytokine and proliferative responses. The D3 variant of a different NS4b epitope 2423 and the D2 variant of the NS4a epitope 2148 induced the largest cytokine response, compared with their respective heterologous sequences in all donors regardless of the primary vaccination serotype. Stimulation with variant peptides also altered the relative frequencies of the various subsets of cells that expressed IFN-gamma, TNF-alpha, MIP-1beta, and combinations of these cytokines. These results indicate that the prior infection history of the individual as well as the serotypes of the primary and heterologous secondary viruses influence the nature of the secondary response. These differences in the effector functions of serotype cross-reactive memory T cells induced by heterologous variant epitopes, which are both quantitative and qualitative, may contribute to the clinical outcome of secondary dengue infection.

CD8-Positive T-Lymphocytes↗

Variation among geographic strains of Aedes albopictus in susceptibility to infection with dengue viruses.

The comparative susceptibility to dengue virus infection of 13 geographic strains of Aedes albopictus was studied by feeding the mosquitoes on a virus-erythrocyte-sugar suspension. Significant variation in susceptibility for each of the four dengue serotypes was observed among the geographic strains. Mosquito strains which were more susceptible to infection with one dengue serotype also were more susceptible to the other dengue serotypes. There was a direct relationship between the amount of virus ingested and the infection rate in a given mosquito strain. A 100-fold difference in oral ID50 was noted between the most and the least susceptible strains. Crossing experiments between susceptible and resistant mosquito strains produced hybrid progeny with intermediate susceptibility. Susceptibility to infection by dengue 2 virus was decreased by selective inbreeding in one strain from 74% to 13% in two generations. Further selection, however, failed to produce a completely resistant line. It appeared that the actual "barrier" to infection was in the mosquito midgut.

Aedes↗

Enhancement of dengue virus infection in monocytes by flavivirus antisera.

Enhanced dengue 2 virus (D2V) infection in suspension cultures of human peripheral blood mononuclear phagocytes (PBL) produced by subneutralizing concentrations of dengue antisera has been described previously. In this study, the enhancement phenomenon was found to be a general property of representative flavivirus antisera. All except one of 24 antisera, which had been raised by 1-3 injections of flaviviruses in rabbits, enhanced the growth of dengue 2 virus in human PBL. Flavivirus antisera showing the greatest level of cross-reactivity against a battery of 42 flavivirus antigens in the hemagglutination-inhibition test were most potent in enhancing dengue replication in PBL cultures. Cross-neutralizing reactivity did not relate to enhanced D2V infection. However nearly one-half of studied flavivirus antisera neutralized D2V at dilutions of 1:10 or 1:20. Heterotypic D2V neutralizing antibody could serve as a "brake" on infection enhancement in vivo. Observations should be made in the field to look for possible enhancement of dengue infection in heterotypic flavivirus immunes.

Adult↗

Dengue virus-specific and flavivirus group determinants identified with monoclonal antibodies by indirect immunofluorescence.

Monoclonal antibodies produced against the four dengue virus serotypes identified four categories of reactions by immunofluorescence: flavivirus group reactive, dengue complex specific, dengue subcomplex specific (DEN-1, DEN-3), and dengue serotype specific. This is the first time that monospecific antibodies have been available for all of these unique antigenic determinants. Hybridoma cell lines producing dengue type-specific antibodies have been deposited in the Hybridoma Cell Bank of the American Type Culture Collection (Rockville, MD) for general distribution.

Animals↗

Epitopic analysis of antigenic determinants on the surface of dengue-2 virions using monoclonal antibodies.

The relative binding sites of dengue serotype-specific, dengue subcomplex-specific, dengue complex-specific, flavivirus subgroup-reactive, and flavivirus group-reactive monoclonal antibody preparations were identified by using competitive antibody binding assays. A dengue complex-specific epitope, capable of mediating infection enhancement, was identified on a 20,000 dalton protein found on intracellular virions. The other epitopes were assigned relative positions on the E glycoprotein by competitive antibody binding. These could be grouped into 3 linkage groups based on the ability of some monoclonal antibodies to block contiguous binding sites. Some antibodies were able to increase or "promote" the binding of antibodies from other linkage groups. These results suggest that a continuum of antigenic reactivities exist on the E glycoprotein of the dengue viruses, and that the conformation of this glycoprotein may be altered after antibody binding.

Aedes↗

Vertical transmission of dengue viruses by mosquitoes of the Aedes scutellaris group.

Seventeen strains of mosquitoes belonging to 12 species in the Aedes scutellaris subgroup were tested for an ability to transmit one or more dengue virus serotype(s) vertically. Strains of virus employed for dengue types 1, 2, 3, and 4 were from Fiji, Bangkok, Burma, and Medan, respectively. After parental females were infected by intrathoracic inoculation, F1 larval and pupal progeny were tested for the presence of virus by inoculating aliquots of triturated suspensions into Toxorhynchites amboinensis mosquitoes. Dengue type 1 was transmitted vertically by 11 strains of mosquitoes representing 8 species with the highest filial infection rates observed for Ae. cooki (1.2%). Vertical transmission of the other dengue virus serotypes was observed for fewer species of mosquitoes, however the filial infection rates of those demonstrating vertical transmission were between 1%-2% for types 2 and 3, and about 0.5% for type 4. Tests with the progeny of individual Ae. cooki and Ae. polynesiensis infected with dengue virus types 1 and 3, respectively, showed that approximately greater than or equal to 50% of the parental females transmitted virus to their progeny. Highest filial infection rates were 6.7% for Ae. cooki and 4.6% for Ae. polynesiensis.

Aedes↗

A simulation model of the epidemiology of urban dengue fever: literature analysis, model development, preliminary validation, and samples of simulation results.

We have developed a pair of stochastic simulation models that describe the daily dynamics of dengue virus transmission in the urban environment. Our goal has been to construct comprehensive models that take into account the majority of factors known to influence dengue epidemiology. The models have an orientation toward site-specific data and are designed to be used by operational programs as well as researchers. The first model, the container-inhabiting mosquito simulation model (CIMSiM), a weather-driven dynamic life-table model of container-inhabiting mosquitoes such as Aedes aegypti, provides inputs to the tranmission model, the dengue simulation model (DENSiM); a description and validation of the entomology model was published previously. The basis of the transmission model is the simulation of a human population growing in response to country- and age-specific birth and death rates. An accounting of individual serologies is maintained by type of dengue virus, reflecting infection and birth to seropositive mothers. Daily estimates of adult mosquito survival, gonotrophic development, and the weight and number of emerging females from the CIMSiM are used to create the biting mosquito population in the DENSiM. The survival and emergence values determine the size of the population while the rate of gonotrophic development and female weight estimates influence biting frequency. Temperature and titer of virus in the human influences the extrinsic incubation period; titer may also influence the probability of transfer of virus from human to mosquito. The infection model within the DENSiM accounts for the development of virus within individuals and its passage between both populations. As in the case of the CIMSiM, the specific values used for any particular phenomenon are on menus where they can be readily changed. It is possible to simulate concurrent epidemics involving different serotypes. To provide a modicum of validation and to demonstrate the parameterization process for a specific location, we compare simulation results with reports on the nature of epidemics and seroprevalence of antibody in Honduras in low-lying coastal urbanizations and Tegucigalpa following the initial introduction of dengue-1 in 1978 into Central America. We conclude with some additional examples of simulation results to give an indication of the types of questions that can be investigated with the models.

Adolescent↗

Risk factors in dengue shock syndrome.

Despite a growing body of evidence predominantly, but not exclusively, from Thailand suggesting that the risk of developing dengue shock syndrome (DSS) is greatest following an anamnestic dengue infection, particularly if the most recent infection was with dengue 2 virus, there continues to be debate about the justification for these claims. This report describes a five-year, prospective study in two townships (suburbs) in Yangon (Rangoon) Myanmar (Burma) in which attempts were made to confirm the data from an earlier prospective study in Thailand and to address some of the criticism of earlier studies. This investigation found the incidence of anamnestic dengue infections in DSS patients to be significantly higher than in the community from which they were drawn and a significantly higher risk of developing DSS following an anamnestic infection (particularly with dengue 2 virus) than following a primary infection with any serotype.

Child↗

Application of geographical information systems to co-analysis of disease and economic resources: dengue and malaria in Thailand.

Two vector-borne communicable diseases, malaria and dengue, are among a number of diseases of particular importance in relation to economic development in Southeast Asia and thus need to be assessed in relation to economic parameters in the region. Geographical Information Systems (GIS) provide one means of comparing disease and resource data versus time and place, to facilitate rapid visualization by planners and administrators. Given that Thailand is a global epicenter of multidrug resistant falciparum malaria and of dengue hemorrhagic fever, both of which are mosquito-borne, application of GIS methods to these two diseases gives opportunity for comparison of resource needs and allocation in relation to disease epidemiologic patterns. This study examined per capita gross provincial product (GPPpc) and health care resources in relation to geographic distribution of malaria and dengue in Thailand. The two diseases vary greatly in overall seasonal patterns and in relation to provincial economic status, and present differing demands on resource utilization: planned integration of control of malaria and dengue could utilize such analyses in relation to resource sharing and consideration of allocative efficiency. The concentration of malaria (and to a lesser extent dengue) along international border areas underscores the desirability of multi-country coordination of disease management and control programs. Because socio-economic and disease data are collected by quite different means and in different time frames, there are some limitations to the dynamic interpolation of these two broad data sets, but useful inferences can be drawn from this approach for application to overall planning, at both national and multi-country levels.

Dengue↗

Imported dengue--United States, 1997 and 1998.

Dengue is a mosquito-transmitted acute viral disease caused by one of four dengue virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). Dengue is endemic in most tropical areas of the world and has occurred in U.S. residents returning from travel to such areas. CDC maintains a laboratory-based passive surveillance system for imported dengue among U.S. residents. The system relies principally on reports by clinicians to state health departments, which forward patient specimens to CDC for diagnostic testing. This report summarizes information about imported dengue cases among U.S. residents for 1997 and 1998, which indicates that most persons with a known travel history probably acquired infection in the Caribbean islands or Asia.

Adolescent↗

[Dengue or acute retroviral syndrome?].

BACKGROUND: The diagnosis of primary HIV infection is a crucial element in the fight against the AIDS epidemic. Clinical manifestations associated with primary infection are nonspecific. Dengue is a possible differential diagnosis. CASE REPORT: A 15-year-old adolescent living in Martinique consulted for a syndrome suggestive of infectious mononucleosis. The annual dengue epidemic was at its acme at this time. Serum was positive for IgM and the diagnosis of dengue was retained. The diagnosis of recent HIV infection was made two months later (unprotected homosexual intercourse two weeks before onset of clinical signs). Retrospective analysis of the earlier samples at the time of the viral syndrome demonstrated that the patient actually had an acute retroviral syndrome. DISCUSSION: The clinical and biological manifestations of dengue and primary HIV infection are nonspecific and similar to those of infectious mononucleosis. Potential exposure to HIV and recent presence in endemic dengue regions (tropical areas in America, Asia and Africa) can provide helpful guidance for differential diagnosis.

Acute Disease↗

Use of a computer model to identify potential hotspots for dengue fever in New Zealand.

AIMS: To describe the areas of potential dengue fever risk in New Zealand for present climatic conditions and projected scenarios of climate change. METHODS: A computer model, the HOTSPOTS System, was developed. This allowed the integration of climatic, topographical, entomological, demographic, trade and travel data to generate spatial information describing vector introduction risk, potential vector distribution and dengue fever risk. RESULTS: Under present climatic conditions, Auckland and Northland, and some coastal areas of other northern parts of the North Island, have a potential risk for dengue outbreaks supported by the vector Aedes albopictus. Greenhouse gas induced climate change could make these areas also receptive to Aedes aegypti--the more efficient tropical dengue vector--and increase the potential distribution of A. albopictus to much of the South Island. CONCLUSIONS: Given the introduction of a competent vector, there is an appreciable risk of dengue fever occurring in New Zealand under present climatic conditions. Greenhouse gas induced climate change would substantially increase the magnitude and spatial extent of this risk.

Climate↗

Dengue virus infection of the central nervous system (CNS): a case report from Brazil.

Dengue infection that is accompanied by unusual complications has been described in Brazil. We report on the presence of dengue virus in the central nervous system (CNS) of a patient who died in 1998 in Rio Grande do Norte, northeast Brazil. DEN-2 viruses were isolated from the brain liver, and lymphnode tissue of a 67-year-old man whose signs and symptoms were those of dengue infection and a secondary immune response. A postmortem revealed nose bleeds a liver that was brownish with yellow areas, and pulmonary and cerebrae congestion. Immunoperoxidase staining showed a dengue antigen-specific positive reaction in the gray matter cells of the cerebrall cortex; a granular citoplasmatic reaction was seen in the neurons. Dengue infection should always be considered as a cause encephalitis in tropical countries, especially in those where the disease is endemic.

Aged↗